INTRODUCTION: Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist that exhibits sedative, analgesic, anxiolytic, and sympatholytic effects without respiratory-drive depression. We prospectively evaluated the use of dexmedetomidine to facilitate the withdrawal of mechanical ventilation and extubation in 5 trauma/surgical intensive-care-unit patients who had failed previous weaning attempts due to agitation and hyperdynamic cardiopulmonary response. METHODS: Intravenous infusion of dexmedetomidine commenced at 0.5 or 0.7 mu g/kg/h without a loading dose. Background sedation and analgesia with propofol, benzodiazepines, and opiates was discontinued or reduced as tolerated. Dexmedetomidine infusion was titrated between 0.2 and 0.7 mu g/kg/h to maintain a stable cardiopulmonary response and modified Ramsay Sedation Score between 2 and 4. RESULTS: Following dexmedetomidine administration, propofol infusion was weaned and discontinued in 4 patients. In the fifth patient, benzodiazepine and opiate infusions were reduced. Ventilatory support in all patients could be weaned to continuous positive airway pressure of 5 cm H2O without agitation, hemodynamic instability, or respiratory decompensation. All patients were extubated while receiving dexmedetomidine infusion (mean dose of 0.32 +/- 0.08 mu g/kg/h). One patient required reintubation for upper-airway obstruction. CONCLUSION: Dexmedetomidine appears to maintain adequate sedation without hemodynamic instability or respiratory-drive depression, and thus may facilitate extubation in agitated difficult-to-wean patients; it therefore deserves further investigation toward this novel use.